Angiotensinogen (AGT) is the precursor of active vasoconstrictive octapeptide angiotensin II (Ang II) in the renin-angiotensin-aldosterone system. Blocking the AGT-converting enzymes in the pathway and the Ang II receptor through pharmacological agents has been proven to be effective in lowering blood pressure (BP) in hypertensive patients. In this study, we developed chemically modified small interfering RNAs (siRNA) to target hepatic AGT mRNA in rats. Lipid nanoparticle encapsulated siRNAs were efficiently delivered to rat liver and resulted in significant reduction in hepatic Agt mRNA levels and plasma AGT concentration without impairing liver function. Single intravenous injection of Agt siRNA led to significant and sustained BP lowering in spontaneous hypertensive rats and in Sprague-Dawley rats, and the effect was maintained by weekly siRNA dosing. Data presented here provide proof-of-feasibility for the use of siRNA technology for inhibition of peripheral AGT levels via hepatic mRNA silencing with beneficial effects on BP in preclinical rat models. Similar approach could be used for validation of novel hypertension hepatic and extrahepatic targets.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/hr.2013.155 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Application of biomass carbon dots in food packaging.
Environ Sci Pollut Res Int
January 2025
College of Materials Science and Engineering, Nanjing Forestry University, Nanjing, 210037, China.
Since its discovery, carbon quantum dots (CDs) have been widely applied in cell imaging, drug delivery, biosensing, and photocatalysis due to their excellent water solubility, chemical stability, fluorescence stability biocompatibility, low toxicity, and preparation cost. However, the low fluorescence yield and poor surface structure limit the application of CDs. Heteroatom doping is considered an ideal method to improve CDs' optical and electrical properties.
View Article and Find Full Text PDFNew semisynthetic α-glucosidase inhibitor from a doubly-chemically engineered extract.
Nat Prod Bioprospect
January 2025
Consejo Nacional de Investigaciones Científicas y Técnicas, Suipacha 531, S2002LRK, Rosario, Argentina.
Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules. Prepared through direct derivatization of natural extracts, they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs. Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent, and their α-glucosidase inhibition properties were compared.
View Article and Find Full Text PDFPolyamide/silica/sodium alginate in-situ composite: Synthesis and application in electrochemical probing for Pb/Cd.
Int J Biol Macromol
January 2025
College of Chemistry and Chemical Engineering, Southwest Petroleum University, Chengdu 610500, PR China; Engineering Research Center of Oilfield Chemistry, Ministry of Education, Chengdu 610500, PR China; Oil & Gas Field Applied Chemistry Key Laboratory of Sichuan Province, Chengdu 610500, PR China. Electronic address:
In this study, polyamide/silica/sodium alginate (SA) composite (PA-Si-SA) was successfully prepared in one-step benzoxazine-isocyanide chemistry (BIC)/sol-gel process at room temperature. The chemical structure and fundamental properties of PA-Si-SA were characterized by FT-IR, solid-state C NMR, XPS, XRD, SEM, BET and TG, etc. The presence of anionic SA and diverse N, O-containing functional segments (amide, tertiary amine, alkyl/phenol -OH, Si-O-Si, and COO) in PA-Si-SA endows it synergistic complexation capability toward Pb and Cd.
View Article and Find Full Text PDFApplication of lanthanum-modified silk fibroin/polyvinyl alcohol film for highly selective defluoridation in brick tea infusion.
Int J Biol Macromol
January 2025
State Key Laboratory of Tea Plant Biology and Utilization, Joint Research Center for Food Nutrition and Health of IHM and Anhui Provincial Key Laboratory of Food Safety Monitoring and Quality Control, Anhui Agricultural University, Hefei 230036, PR China; College of Food and Nutrition, Anhui Agricultural University, Hefei 230036, PR China. Electronic address:
To mitigate the risk associated with water-soluble fluoride in tea and to have less influence on the contents of tea infusion, a highly selective lanthanum modified silk fibroin (SF) and polyvinyl alcohol (PVA) composite film (SF/PVA-La) was prepared to remove fluoride from brick tea infusion. Notably, SF/PVA-La could remove about 48 % of the fluoride from in brick tea infusion within 30 min. Importantly, the reduction in total tea polyphenols in brick tea did not exceed 10 %, and the reduction in caffeine was only 0.
View Article and Find Full Text PDFLinking new national active biomonitoring data with stream macroinvertebrate communities suggests large-scale effects of toxic contamination on freshwater ecosystems.
Sci Total Environ
January 2025
INRAE, UR RiverLy, Villeurbanne F-69625, France.
Since recent years, an increasingly large number of toxic chemicals enters watercourses threatening freshwater biodiversity. But ecological studies still poorly document the quantitative patterns linking exposure to complex mixture of toxic chemicals and species communities' integrity in the field. In this context, French monitoring authorities have recently deployed at a national scale in situ biotests using the feeding inhibition of the crustacean Gammarus as toxicity indicator.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!